Morphological and functional abnormalities of hippocampus in APC mice.

In the present study, we examined morphology and function of hippocampus in the APC mouse. Expression levels of the APC mRNA and protein were both identical in the hippocampus of the APC and APC mice. The dentate gyrus of the APC hippocampus was thicker, and has more densely-populated granule cells in the APC mouse hippocampus.

Validation and application of a novel APC antibody in western blotting, immunoprecipitation, and immunohistochemistry.

Adenomatous polyposis coli (APC) is a large protein with multiple binding partners, suggesting diverse functions besides its well-known role in the destruction of β-catenin. To elucidate these complex functions, it is crucial to evaluate the precise subcellular distribution of APC within a cell and tissue. However, most of the commercially available anti-APC antibodies can only be used for limited applications, resulting in the use of independently generated antibodies.

BRI2 as an anti-Alzheimer gene.

There are several theories regarding the etiologies of Alzheimer disease (AD). Considering that all genes responsible for familial AD are amyloid protein precursor (APP) or APP metabolizing enzymes, surely aberrant APP metabolism is crucial to pathogenesis of AD. BRI2, a type II transmembrane protein, binds APP and inhibits all α, β, and γ pathways of APP proteolysis.

A disturbance of intestinal epithelial cell population and kinetics in APC1638T mice.

The adenomatous polyposis coli (APC) is a multifunctional protein as well as a tumor suppressor. To determine the functions of the C-terminal domain of APC, we explored APC (APC1638T) mice that express a truncated APC lacking the C-terminal domain. The APC1638T mice were tumor free and exhibited growth retardation.

Translocated in liposarcoma regulates the distribution and function of mammalian enabled, a modulator of actin dynamics.

Translocated in liposarcoma/fused in sarcoma (TLS/FUS) is an RNA-binding protein that regulates the splicing pattern of mRNA transcripts and is known to cause a type of familial amyotrophic lateral sclerosis (ALS). In the absence of TLS, Mammalian enabled (Mena), an actin-regulatory protein and a target of TLS, undergoes preferential alternative splicing. In the present study, we show that the ablation of TLS dysregulates the subcellular location and functions of Mena.

Proteomic characterization of a mouse model of familial Danish dementia.

A dominant mutation in the ITM2B/BRI2 gene causes familial Danish dementia (FDD) in humans. To model FDD in animal systems, a knock-in approach was recently implemented in mice expressing a wild-type and mutant allele, which bears the FDD-associated mutation. Since these FDD(KI) mice show behavioural alterations and impaired synaptic function, we characterized their synaptosomal proteome via two-dimensional differential in-gel electrophoresis.

β- but not γ-secretase proteolysis of APP causes synaptic and memory deficits in a mouse model of dementia.

A mutation in the BRI2/ITM2b gene causes loss of BRI2 protein leading to familial Danish dementia (FDD). BRI2 deficiency of FDD provokes an increase in amyloid-β precursor protein (APP) processing since BRI2 is an inhibitor of APP proteolysis, and APP mediates the synaptic/memory deficits in FDD. APP processing is linked to Alzheimer disease (AD) pathogenesis, which is consistent with a common mechanism involving toxic APP metabolites in both dementias.

Increased AβPP processing in familial Danish dementia patients.

An autosomal dominant mutation in the BRI2/ITM2B gene causes Familial Danish Dementia (FDD). We have generated a mouse model of FDD, called FDDKI, genetically congruous to the human disease. These mice carry one mutant and one wild type Bri2/Itm2b allele, like FDD patients.

APP heterozygosity averts memory deficit in knockin mice expressing the Danish dementia BRI2 mutant.

An autosomal dominant mutation in the BRI2/ITM2B gene causes familial Danish dementia (FDD). Analysis of FDD(KI) mice, a mouse model of FDD genetically congruous to the human disease since they carry one mutant and one wild-type Bri2/Itm2b allele, has shown that the Danish mutation causes loss of Bri2 protein, synaptic plasticity and memory impairments. BRI2 is a physiological interactor of Aβ-precursor protein (APP), a gene associated with Alzheimer disease, which inhibits processing of APP.

Danish dementia mice suggest that loss of function and not the amyloid cascade causes synaptic plasticity and memory deficits.

According to the prevailing "amyloid cascade hypothesis," genetic dementias such as Alzheimer's disease and familial Danish dementia (FDD) are caused by amyloid deposits that trigger tauopathy, neurodegeneration, and behavioral/cognitive alterations. To efficiently reproduce amyloid lesions, murine models of human dementias invariably use transgenic expression systems. However, recent FDD transgenic models showed that Danish amyloidosis does not cause memory defects, suggesting that other mechanisms cause Danish dementia.

Generation and initial characterization of FDD knock in mice.

Background: Mutations in the integral membrane protein 2B, also known as BRI(2), a type II trans-membrane domain protein cause two autosomal dominant neurodegenerative diseases, Familial British and Danish Dementia. In these conditions, accumulation of a C-terminal peptide (ABri and ADan) cleaved off from the mutated precursor protein by the pro-protein convertase furin, leads to amyloid deposition in the walls of blood vessels and parenchyma of the brain. Recent advances in the understanding of the generation of amyloid in Alzheimer's disease has lead to the finding that BRI(2) interacts with the Amyloid Precursor Protein (APP), decreasing the efficiency of APP processing to generate Abeta.

CD74 interacts with APP and suppresses the production of Abeta.

Background: Alzheimer disease (AD) is characterized by senile plaques, which are mainly composed of beta amyloid (Abeta) peptides. Abeta is cleaved off from amyloid precursor protein (APP) with consecutive proteolytic processing by beta-secretase and gamma-secretase.

Results: Here, we show that CD74, the invariant chain of class II major histocompatibility complex, interacts with APP and serves as a negative regulator of Abeta.

Maturation of BRI2 generates a specific inhibitor that reduces APP processing at the plasma membrane and in endocytic vesicles.

Processing of the amyloid-β (Aβ) precursor protein (APP) has been extensively studied since it leads to production of Aβ peptides. Toxic forms of Aβ aggregates are considered the cause of Alzheimer's disease (AD). On the other end, BRI2 is implicated in APP processing and Aβ production.

BRI3 inhibits amyloid precursor protein processing in a mechanistically distinct manner from its homologue dementia gene BRI2.

Alzheimer disease (AD) is characterized by senile plaques, which are mainly composed of beta amyloid (Abeta) peptides. Abeta is cleaved off from amyloid precursor protein (APP) with consecutive proteolytic processing: beta-secretase, followed by gamma-secretase. Here, we show that BRI3, a member of the BRI gene family that includes the familial British and Danish dementia gene BRI2, interacts with APP and serves as an endogenous negative regulator of Abeta production.

BRI2 inhibits amyloid beta-peptide precursor protein processing by interfering with the docking of secretases to the substrate.

Genetic alterations of amyloid beta-peptide (Abeta) production caused by mutations in the Abeta precursor protein (APP) cause familial Alzheimer's disease (AD). Mutations in BRI2, a gene of undefined function, are linked to familial British and Danish dementias, which are pathologically and clinically similar to Alzheimer's disease. We report that BRI2 is a physiological suppressor of Abeta production.

The familial dementia BRI2 gene binds the Alzheimer gene amyloid-beta precursor protein and inhibits amyloid-beta production.

Alzheimer disease (AD), the most common senile dementia, is characterized by amyloid plaques, vascular amyloid, neurofibrillary tangles, and progressive neurodegeneration. Amyloid is mainly composed by amyloid-beta (A(beta)) peptides, which are derive from processing of the beta-amyloid precursor protein (APP), better named amyloid-beta precursor protein (A(beta)PP), by secretases. The A(beta)PP intracellular domain (AID), which is released together with A(beta), has signaling function, since it modulates apoptosis and transcription.

Cytoplasmic tail adaptors of Alzheimer's amyloid-beta protein precursor.

Alzheimer's disease is characterized pathologically by senile plaques in the brain. The major component of senile plaques is amyloid-beta (Abeta), which is cleaved from Alzheimer's Abeta protein precursor (AbetaPP). Recently, information regarding the cytoplasmic tail of AbetaPP has started to emerge, opening up various insights into the physiological roles of AbetaPP and its pathological role in Alzheimer's disease.

Gadd45 beta mediates the NF-kappa B suppression of JNK signalling by targeting MKK7/JNKK2.

NF-kappa B/Rel transcription factors control apoptosis, also known as programmed cell death. This control is crucial for oncogenesis, cancer chemo-resistance and for antagonizing tumour necrosis factor alpha (TNFalpha)-induced killing. With regard to TNFalpha, the anti-apoptotic activity of NF-kappa B involves suppression of the c-Jun N-terminal kinase (JNK) cascade.

Amyloid beta protein precursor (AbetaPP), but not AbetaPP-like protein 2, is bridged to the kinesin light chain by the scaffold protein JNK-interacting protein 1.

Proteolytic processing of amyloid beta protein precursor (AbetaPP) generates peptides that regulate normal cell signaling and are implicated in Alzheimer's disease pathogenesis. AbetaPP processing also occurs in nerve processes where AbetaPP is transported from the cell body by kinesin-I, a microtubule motor composed of two kinesin heavy chain and two kinesin light chain (Klc) subunits. AbetaPP transport is supposedly mediated by the direct AbetaPP-Klc1 interaction.

Cardiac sarcoidosis: an overview of management for the patient requiring oral and maxillofacial surgery.

Purpose: The study goal was to present a current definition of sarcoidosis and an overview of cardiac involvement and implications in perioperative management of cardiac sarcoidosis.

Materials And Methods: Materials included a retrospective review of 4 patients with cardiac sarcoidosis who underwent minor oral surgery. Laboratory data, medical data, and data obtained through monitoring the patient's general condition related to the surgery were critically analyzed.

JNK-interacting protein-1 promotes transcription of A beta protein precursor but not A beta precursor-like proteins, mechanistically different than Fe65.

Processing of the amyloid beta protein precursor (A beta PP) by the beta and gamma secretases leads to the production of two small peptides, amyloid beta and the A beta PP intracellular domain (AID, or called elsewhere AICD). Whereas the role of amyloid beta in the pathogenesis of Alzheimer's disease has been studied extensively, only recently has information begun to accumulate as to the role of AID. Functions identified for AID include its ability to trigger apoptosis and a role in regulating gene transcription, particularly in combination with the A beta PP binding protein Fe65.